This project is concerned with the basic physiological processes responsible for regulating the amount of synaptic transmitter released presynaptically by a nerve impulse, and the duration of postsynaptic action. Some experiments will focus on the membrane processes responsible for facilitation of synaptic transmission following neuronal activity. Voltage-clamp techniques and the photochemical detection of intracellular calcium will be used to determine whether electrically excitable membrane channels themselves facilitate, and whether an increased level of intracellular calcium can influence any membrane channels in a way that could lead to synaptic facilitation. The significance of these experiments lies in the central role that synaptic plasticity plays in adaptive behaviors. Additional experiments will focus on the pre- or postsynaptic factors regulating the time-course of inhibitory postsynaptic current following a presynaptic nerve impulse. The rates of transmitter release and uptake, and the postsynaptic channel lifetime will be estimated using the electrophysiological method of voltage-clamping the postsynaptic current and the biophysical methods of voltage-step relaxation and fluctuation analyses of postsynaptic current. These experiments will provide tools for the analysis of the mechanism of anticonvulsants and tranquilizers, which appear to operate by prolonging synaptic inhibition.